Single-Nucleus Transcriptomic Atlas of Human Pericoronary Epicardial Adipose Tissue in Normal and Pathological Conditions.

BACKGROUND: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. METHODS: We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. RESULTS: Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 and SEMA3B were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. CONCLUSIONS: We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.

A Multicenter Study of the Mid-term Outcomes of Patients with Uncomplicated Type B Aortic Dissection After Distal Porous Talos Stent-Graft Implantation.

BACKGROUND: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia (SCI). This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety end point was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy end point was treatment success at 12 months postoperation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at 4 levels, and SCI was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.

Mid-term results of a prospective study for aortic dissection with a gutter-plugging chimney stent graft.

OBJECTIVES: Our goal was to access early and mid-term outcomes of a gutter-plugging chimney stent graft for treatment of Stanford type B aortic dissections in the clinical trial Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology (PATENCY). METHODS: Between October 2018 and March 2022, patients with Stanford type B aortic dissections were treated with the Longuette chimney stent graft in 26 vascular centres. The efficiency and the incidence of adverse events over 12 months were investigated. RESULTS: A total of 150 patients were included. The technical success rate was 99.33% (149/150). The incidence of immediate postoperative endoleak was 5.33% (8/150, type I, n = 6; type II, n = 1; type IV, n = 1) neurologic complications (stroke or spinal cord ischaemia); the 30-day mortality was 0.67% (1/150) and 1.33% (2/150), respectively. During the follow-up period, the median follow-up time was 11.67 (5-16) months. The patent rate of the Longuette graft was 97.87%. Two patients with type I endoleak underwent reintervention. The follow-up rate of the incidence of retrograde A type aortic dissection was 0.67% (1/150). There was no paraplegia, left arm ischaemia or stent migration. CONCLUSIONS: For revascularization of the left subclavian artery, the Longuette chimney stent graft can provide an easily manipulated, safe and effective endovascular treatment. It should be considered a more efficient technique to prevent type Ia endoleak. Longer follow-up and a larger cohort are needed to validate these results. CLINICAL TRIAL REGISTRY NUMBER: NCT03767777.

Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root.

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell-type-specific transcriptomic and cis-regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

In Situ Fenestration and Carotid-Subclavian Bypass for Left Subclavian Artery Revascularization During Thoracic Endovascular Aortic Repair.

PURPOSE: To evaluate the safety and feasibility of left subclavian artery (LSA) revascularization techniques during thoracic endovascular aortic repair (TEVAR)-the in situ needle fenestration (ISNF) technique and the carotid-subclavian bypass (CS-Bp)-for complicated aortic pathologies. METHODS: A retrospective single-center observational study was conducted to identify all patients with thoracic aortic pathologies who underwent TEVAR with LSA revascularization using either CS-Bp or ISNFs from January 2014 to December 2020. RESULTS: One hundred and twelve consecutive patients who received TEVAR with LSA revascularization were included. Among them, 69 received CS-Bp and 43 received ISNF (29 using the Futhrough adjustable puncture needles, 14 using the binding stent-graft puncture systems). Technical success, defined as achieving aortic arch pathology exclusion and LSA preservation, was attained in 99.1% patients. Early mortality was 0.9%. Major adverse events within 30 days, including one cerebral hemorrhage, one cervical incision hemorrhage, one stroke and two paraplegia, were exclusively observed in the CS-Bp group. Immediate type I, II and III endoleaks occurred in 0%, 4.7% and 2.3% in the ISNF group, respectively, compared to 0%, 2.9% and 0% in the CS-Bp group.One hundred and eight (97.2%) patients were available for follow-up at a median 50 (maiximum of 103) months, revealing a LSA patency rates of 99.1%. Six patients died during follow-ups-five in the CS-Bp group and one in the ISNF group. Cause of death include one aortic-related stent-graft infection, three non-related and two with unknow causes. The survival exhibited no significantly different between the ISNF (97.7%) and CS-Bp (89.9%) groups (p = 0.22). CONCLUSIONS: Both CS-Bp and ISNF are feasible techniques for LSA reconstruction in TEVAR. ISNF, whether using Futhrough or BPS, seems to be competitive with CS-Bp.

Efficacy of Endovascular Repair Using Single Left Common Carotid Artery Stent Combined with Castor Single-Branched Stent-Graft in the Treatment of Regional Diseases of Zone 2 of the Aorta.

PURPOSE: To observe the short-term efficacy of thoracic endovascular aortic repair (TEVAR) using a single left common carotid artery chimney stent combined with a Castor single-branched stent-graft (SC-TEVAR) in the treatment of zone 2 (Z2) aortic diseases. MATERIALS AND METHODS: To conduct a retrospective analysis of 20 patients with Z2 aortic diseases who were treated in our department from June 2021 to April 2022. The lesions included true aortic degenerative aneurysms with diameter ≥5.0 cm and penetrating aortic ulcers with depth >1.0 cm or basal width >2.0 cm. All 20 patients accepted the SC-TEVAR treatment, which was a new hybrid method to assure the flow of the left common carotid artery (LCCA) and left subclavian artery (LSA). This method was defined as a concomitant chimney stent for LCCA and a Castor single-branched stent graft for the aorta and LSA. The baseline data and intraoperative data were collected to evaluate the safety and efficacy of this method. The patency of the target blood vessel and any associated complications were evaluated at 1 and 6 months postoperatively, to analyze the safety and efficacy of this new method. RESULTS: After discharge from the hospital, all patients were followed up by a specific follow-up team. At 6 monthly follow-up period, there were no cardiac events, stroke, hemiplegia, type I endoleak, type II endoleak, proximal stent graft-induced new entries, distal stent graft-induced new entries, wound infection, or bleeding. Only 1 patient developed an inguinal wound hematoma and got conservative treatment. Importantly, no patients developed stenosis or occlusion of the LCCA or LSA. The patency of branched arteries was 100%. The technical success rate was 90%. CONCLUSION: SC-TEVAR appears to be a new and relatively simple, safe, and effective treatment for Z2 aortic diseases. CLINICAL IMPACT: This was a single-center retrospective cohort study. A total of 20 patients with zone 2 aortic diseases accepted a new hybrid surgical method named SC-TEVAR. This method was not complicated and could be finished with only 3 peripheral artery exposure. The result showed no mortality, 100% patency of the branch artery, and 90% of technical success in 6 months of follow-up time. SC-TEVAR showed a satisfactory result in this retrospective study and could be promoted as an easy method to treat zone 2 aortic diseases.

Evaluation of associations between outflow morphology and rupture risk of abdominal aortic aneurysms.

PURPOSE: This study aimed to evaluate the association between the outflow morphology and abdominal aortic aneurysm (AAA) rupture risk, to find risk factors for future prediction models. MATERIALS AND METHODS: We retrospectively analyzed 46 patients with ruptured AAAs and 46 patients with stable AAAs using a 1:1 match for sex, age, and maximum aneurysm diameter. The chi-square test, paired t-test, and Wilcoxon signed-rank test were used to compare variables. Logistic regression was performed to evaluate variables potentially associated with AAA rupture. Receiver operating characteristic curve analysis and the area under the curve (AUC) were used to assess the regression models. RESULTS: Ruptured AAAs had a shorter proximal aortic neck (median (interquartile range, IQR): 24.0 (9.4-34.2) mm vs. 33.3 (20.0-52.8) mm, p = 0.004), higher tortuosity (median(IQR): 1.35 (1.23-1.49) vs. 1.29 (1.23-1.39), p = 0.036), and smaller minimum luminal area of the right common iliac artery (CIA) (median (IQR): 86.7 (69.9-126.4) mm2 vs. 118.9 (86.3-164.1)mm2, p = 0.001) and left CIA (median(IQR): 92.2 (67.3,125.1) mm2 vs. 110.7 (80.12, 161.1) mm2, p = 0.010) than stable AAA did. Multiple regression analysis demonstrated significant associations of the minimum luminal area of the bilateral CIAs (odds ratio [OR] = 0.996, 95 % confidence interval [CI] 0.991-0.999, p = 0.037), neck length (OR = 0.969, 95 % CI 0.941-0.993, p = 0.017), and aneurysm tortuosity (OR = 1.031, 95 % CI 1.003-1.063, p = 0.038) with ruptured AAAs. The AUC of this regression model was 0.762 (95 % CI 0.664-0.860, p < 0.001). CONCLUSIONS: The smaller minimum luminal area of the CIA is associated with an increased risk of rupture. This study highlights the potential of utilizing outflow parameters as novel and additional tools in risk assessment. It also provides a compelling rationale to further intensify research in this area.

Elongation of the proximal descending thoracic aorta and associated hemodynamics increase the risk of acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (ATBAD) is a life-threatening aortic disease. However, little information is available on predicting and understanding of ATBAD. OBJECTIVE: The study sought to explore the underlying mechanism of ATBAD by analyzing the morphological and hemodynamic characteristics related to aortic length. METHODS: The length and tortuosity of the segment and the whole aorta in the ATBAD group (n= 163) and control group (n= 120) were measured. A fixed anatomic landmark from the distal of left subclavian artery (LSA) to the superior border of sixth thoracic vertebra was proposed as the proximal descending thoracic aorta (PDTA), and the dimensionless parameter, length ratio, was introduced to eliminate the individual differences. The significant morphological parameters were filtrated and the associations between parameters were investigated using statistical approaches. Furthermore, how aortic morphology influenced ATBAD was explored based on idealized aortic models and hemodynamic-related metrics. RESULTS: The PDTA length was significantly increased in the ATBAD group compared with the control group and had a strong positive correlation with the whole aortic length (r= 0.89). The length ratio (LR2) and tortuosity (T2) of PDTA in the ATBAD group were significantly increased (0.15 ± 0.02 vs 0.12 ± 0.02 and 1.73 ± 0.48 vs 1.50 ± 0.36; P< 0.001), and LR2 was positive correlation with T2 (r= 0.73). In receiver-operating curve analysis, the area under the curve was 0.835 for LR2 and 0.641 for T2. Low and oscillatory shear (LOS) was positive correlation with LR2, and the elevated LOS occurred in the distal of LSA. CONCLUSION: Elongation of PDTA is associated with ATBAD, and the length ratio is a novel predictor. Elongated PDTA induced more aggressive hemodynamic forces, and high LOS regions may correspond to the entry tear location. The synergy of the morphological variation and aggressive hemodynamics creates contributory conditions for ATBAD.

Timing of Intervention and Long-Term Outcomes of Type B Aortic Intramural Hematoma with Intimal Disruption at Admission.

BACKGROUND: To compare the 30-day and long-term outcomes between patients with concomitant type B intramural hematoma and intimal disruption upon admission who underwent endovascular repair in the acute or subacute phases. METHODS: Data were extracted from January 1, 2010, to December 31, 2019. Logistic regression and Cox regression were performed to evaluate the impact of timing of intervention on 30-day and long-term outcomes, respectively. RESULTS: The study included 241 patients, among which 159 were in the acute group. No significant difference was observed in 30-day mortality (0.6% vs. 0%, P = 1), 30-day complication rate (2.5% vs. 1.2%, P = 0.664), long-term all-cause mortality (10.7% vs. 7.3%, P = 0.540), and aortic reintervention rate (2.5% vs. 2.4%, P = 1) between the acute and subacute group. In multivariable analysis, the timing of intervention was not associated with 30-day mortality (odds ratio (OR) = 0, 95% confidence interval CI: 0-Inf, P = 0.999), 30-day complication (OR = 0.30, 95% CI: 0.02-3.77, P = 0.348), long-term mortality (hazard ratio = 0.56, 95% CI: 0.20-1.61, P = 0.283), and aortic reintervention (OR = 0.97, 95% CI: 0.15-6.08, P = 0.970). CONCLUSIONS: For patients with concomitant type B intramural hematoma and intimal disruption upon admission, there is no significant difference in 30-day and long-term outcomes between those who undergo endovascular treatment in the acute or subacute phase.

Physics-informed neural networks (PINNs) for 4D hemodynamics prediction: An investigation of optimal framework based on vascular morphology.

Hemodynamic parameters are of great significance in the clinical diagnosis and treatment of cardiovascular diseases. However, noninvasive, real-time and accurate acquisition of hemodynamics remains a challenge for current invasive detection and simulation algorithms. Here, we integrate computational fluid dynamics with our customized analysis framework based on a multi-attribute point cloud dataset and physics-informed neural networks (PINNs)-aided deep learning modules. This combination is implemented by our workflow that generates flow field datasets within two types of patient personalized models - aorta with fine coronary branches and abdominal aorta. Deep learning modules with or without an antecedent hierarchical structure model the flow field development and complete the mapping from spatial and temporal dimensions to 4D hemodynamics. 88,000 cases on 4 randomized partitions in 16 controlled trials reveal the hemodynamic landscape of spatio-temporal anisotropy within two types of personalized models, which demonstrates the effectiveness of PINN in predicting the space-time behavior of flow fields and gives the optimal deep learning framework for different blood vessels in terms of balancing the training cost and accuracy dimensions. The proposed framework shows intentional performance in computational cost, accuracy and visualization compared to currently prevalent methods, and has the potential for generalization to model flow fields and corresponding clinical metrics within vessels at different locations. We expect our framework to push the 4D hemodynamic predictions to the real-time level, and in statistically significant fashion, applicable to morphologically variable vessels.

Hemodynamics of different configurations of the left subclavian artery parallel stent graft for thoracic endovascular aortic repair.

BACKGROUND AND OBJECTIVE: Parallel (chimney and periscope) graft technique is an effective approach for left subclavian artery (LSA) reconstruction in patients treated by thoracic endovascular aortic repair (TEVAR) for the inadequate landing zone. However, certain stent graft (SG) configurations may promote thrombosis and reduce distal blood flow, increasing risks of cerebral infarction and reintervention. METHODS: In this paper, we first attempt to systematically evaluate the hemodynamic performances of different parallel graft techniques as potential determinants of complication risks. Based on the patient-specific 3D aortic geometry undergoing parallel graft technique, fifteen models in total for five kinds of LSA branched SG configurations (Forward, Backward, Extended, Elliptical and Periscopic) were designed virtually, and the hemodynamic discrepancies between them were analyzed by computational fluid dynamics. RESULTS: Results show that flow rate of patients undergoing periscope technique reduces by half compared with chimney technique, suggesting that periscope SG may cause more serious flow obstruction to LSA, leading to stroke. For chimney stent structure, the extension length 0has little influence on energy loss and other parameters. Conversely, hemodynamic differences between the retrograde curvature and the antegrade curvature are significant (time average WSS: 47.07%), so the retrograde curvature might prompt SG displacement. Furthermore, the flatter chimney SG induces more aggressive hemodynamic forces, among which the difference of the maximum WSS between the flatter SG and nearly round SG reaches 65.56%, leading to the greater risk of vascular wall damage. CONCLUSIONS: Results obtained might provide suggestions for physicians to formulate appropriate parallel graft technique schemes in TEVAR.

Single-Center Preliminary Experience with Gutter-Plugging Chimney Stent-Graft for Aortic Dissection.

PURPOSE: To report the early 2-year results and experience of a novel gutter-plugging chimney stent-graft in a single center that participated in the clinical trial of Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology. MATERIALS AND METHODS: Patients diagnosed with aortic dissection were treated with the novel chimney stent-grafts named Longuette™ for the left subclavian artery revascularization. Primary study outcomes were the incidence of freedom from major adverse events within 30 days and success rate of the operation over 12 months. RESULTS: A total of 34 patients were enrolled between September 2019 and December 2020. The immediate technical success rate (stent-grafts successfully deployed without fast-flow type Ia or type III endoleak intraoperatively) was 100%, and there were no conversions to open repair. Type Ia and type II endoleaks were noted in three patients (8.8%) and one patient (2.9%) at discharge, respectively. One patient (2.9%) with type Ia endoleak underwent coil embolization at 12 months because of false lumen dilation, and one (2.9%) case of type Ia endoleak resolved spontaneously at 24 months. One chimney stent (2.9%) was revealed with stenosis at discharge and occluded with thrombosis at 6 months postoperatively. During the 2-year follow-up, there was no death, rupture, stroke, paraplegia, left arm ischemia, retrograde dissection, stent-graft induced new entry, or stent migration. CONCLUSION: The initial results of the Longuette™ stent-graft for revascularization of the left subclavian artery are encouraging with a high technical success rate. Further multicenter follow-up outcomes are required to assess the long-term durability. LEVEL OF EVIDENCE: Level 4, Case Series.

Engineering the maturation of stem cell-derived cardiomyocytes.

The maturation of human stem cell-derived cardiomyocytes (hSC-CMs) has been a major challenge to further expand the scope of their application. Over the past years, several strategies have been proven to facilitate the structural and functional maturation of hSC-CMs, which include but are not limited to engineering the geometry or stiffness of substrates, providing favorable extracellular matrices, applying mechanical stretch, fluidic or electrical stimulation, co-culturing with niche cells, regulating biochemical cues such as hormones and transcription factors, engineering and redirecting metabolic patterns, developing 3D cardiac constructs such as cardiac organoid or engineered heart tissue, or culturing under in vivo implantation. In this review, we summarize these maturation strategies, especially the recent advancements, and discussed their advantages as well as the pressing problems that need to be addressed in future studies.

Endovascular aortic arch repair with chimney technique for pseudoaneurysm.

BACKGROUND: Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. METHODS: A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. RESULTS: The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. CONCLUSION: For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

Association of Ductus Diverticulum and Acute Type B Aortic Dissection.

RATIONALE AND OBJECTIVES: An anatomic association between ductus diverticulum and the primary entry tear in type B aortic dissection was observed. The aim was to reveal the association between ductus diverticulum and acute type B aortic dissection. MATERIALS AND METHODS: A matched case-control study was conducted. Case subjects were extracted from consecutive patients with aortic dissection in the emergency department during 2019; the control subjects were extracted from consecutive patients without major aortic disease during 2019. 1:1 matching was performed for age, sex, and comorbidity, the prevalence of ductus diverticulum was compared, and conditional logistic regression was performed to reveal the association of ductus diverticulum and acute type B aortic dissection. In addition, the anatomic association between the ductus diverticulum and the primary entry tear was assessed in extracted cases, and baseline parameters were compared between dissection patients with or without ductus diverticulum. RESULTS: 128 cases and 402 control subjects were extracted. 86 pairs were formed after matching, and the proportion of ductus diverticulum (19.8% vs 1.2%, p < 0.001) was higher in the case group. Conditional logistic regression revealed ductus diverticulum(OR = 22.04, 95%CI: 2.81-172.76, p = 0.003) as an independent predictor for acute type B aortic dissection. Besides, the ductus diverticulum has an anatomic association with the primary entry tear (OR = 4.22, 95%CI: 1.46-12.25, p = 0.008), and dissection patients with ductus diverticulum were younger (47.9 vs 54.4, p = 0.015) than dissection patients without ductus diverticulum. CONCLUSION: Ductus diverticulum is common in acute type B aortic dissection and is independently associated with acute type B aortic dissection.

EphrinB2 promotes the human aortic smooth muscle cell growth and migration via mediating F-actin remodeling.

OBJECTIVES: To evaluate the potential effect of EphrinB2 in human thoracic aortic dissection (TAD) and to illustrate the mechanisms governing the role of EphrinB2 in the growth of human aortic smooth muscle cells (HASMC). METHODS: In the study, EphrinB2 expression was investigated by qRT-PCR and immunohistochemistry in 12 pairs of TAD and adjacent human tissues. HASMCs were used for in vitro experiments. Next, EphrinB2 overexpression and depletion in HASMCs were established by EphrinB2-overexpressing vectors and small interfering RNA, respectively. The transfection efficiency was evaluated by qRT-PCR and Western blot. The effects of overexpression and depletion of EphrinB2 on cell proliferation, migration, and invasion were tested in vitro. Cell Counting Kit-8, flow cytometry and transwell migration/invasion, and wound healing assay were used to explore the function of EphrinB2 on HASMC cell lines. The relationship between EphrinB2 and F-actin was assessed by Western blot, immunofluorescence, and Co-IP. RESULTS: We found that EphrinB2 was a prognostic biomarker of TAD patients. Moreover, EphrinB2 expression negatively correlated to aortic dissection tissues, and disease incidence of males, suggesting that EphrinB2 might act as a TAD suppressor by promoting proliferation or decreasing apoptosis in HASMC. Next, over-expression of EphrinB2 in HASMC lines drove cell proliferation, migration, and invasion, and inhibited apoptosis while knockdown EphrinB2 showed the opposite phenomenon, respectively. Furthermore, the level of F-actin in mRNA, protein, and distribution in HASMC cell lines highly matched with the expression of EphrinB2, which indicated that EphrinB2 could mediate the HASMC cytoskeleton via inducing F-actin. CONCLUSIONS: In conclusion, our results first provided the pivotal role of EphrinB2 in HASMC proliferation initiated by mediating F-actin and demonstrated a prognostic biomarker and the potential targets for therapy to prevent thoracic aortic dissection.

Molecular characterization and clinical investigation of patients with heritable thoracic aortic aneurysm and dissection.

OBJECTIVES: Thoracic aortic aneurysm and dissection has a genetic predisposition and a variety of clinical manifestations. This study aimed to investigate the clinical and molecular characterizations of patients with thoracic aortic aneurysm and dissection and further explore the relationship between the genotype and phenotype, as well as their postoperative outcomes. METHODS: A total of 1095 individuals with thoracic aortic aneurysm and dissection admitted to our hospital between 2013 and 2022 were included. Next-generation sequencing and multiplex ligation-dependent probe amplification were performed, and mosaicism analysis was additionally implemented to identify the genetic causes. RESULTS: A total of 376 causative variants were identified in 83.5% of patients with syndromic thoracic aortic aneurysm and dissection and 18.7% of patients with nonsyndromic thoracic aortic aneurysm and dissection, including 8 copy number variations and 2 mosaic variants. Patients in the "pathogenic" and "variant of uncertain significance" groups had younger ages of aortic events and higher aortic reintervention risks compared with genetically negative cases. In addition, patients with FBN1 haploinsufficiency variants had shorter reintervention-free survival than those with FBN1 dominant negative variants. CONCLUSIONS: Our data expanded the genetic spectrum of heritable thoracic aortic aneurysm and dissection and indicated that copy number variations and mosaic variants contributed to a small proportion of the disease-causing alterations. Moreover, positive genetic results might have a possible predictive value for aortic event severity and postoperative risk stratification.

Surgical treatment patterns and clinical outcomes of type B aortic dissection involving the aortic arch.

OBJECTIVE: In the present report, we have described the outcomes of endovascular repair, hybrid arch repair, and open surgical repair for type B dissection involving the aortic arch (B1-2, D). METHODS: Cases of endovascular repair, hybrid arch repair, and open surgical repair performed between January 2015 and December 2019 for aortic dissection designated as B1-2, D by the Society for Vascular Surgery/Society of Thoracic Surgeons classification were retrospectively analyzed. The primary end point was all-cause mortality at follow-up. The secondary end points included early mortality, early morbidities, and aortic-related late events. Kaplan-Meier curves were created to analyze survival from all-cause mortality and freedom from aortic-related late events in the endovascular, hybrid, and open groups. Propensity score matching and stratification (stratified by proximal dissection extension: B1, D and B2, D) were performed as sensitivity analyses to compare the outcomes among the three treatment patterns after controlling for major confounders. RESULTS: The present study included 151 patients (men, 79.5%; mean age, 47.3 ± 10.5 years), with 72 (47.7%) in the endovascular group, 46 (30.5%) in the hybrid group, and 33 (21.8%) in the open group. No significant difference was noted in early mortality between the endovascular, hybrid, and open groups (1.4% vs 2.2% vs 3.0%; P = .791). The incidence of early endoleak was significantly greater (33.3% vs 13.0% vs 6.1%; P = .002) and the incidence of renal function deterioration was less (4.2% vs 26.1% vs 24.2%; P = .001) after endovascular repair vs hybrid arch repair and open surgery. After a median follow-up of 40.0 months (range, 0-84.0 months), no significant differences were found in all-cause mortality (5.6% vs 4.3% vs 3.0%; P = 1.0), aortic-related late events (16.7% vs 15.2% vs 12.1%; P = .834), or late endoleak (9.7% vs 4.3% vs 6.1%; P = .630) after endovascular, hybrid, and open surgery. The propensity score matching and stratification analyses displayed consistent outcomes for early mortality, all-cause mortality, and aortic-related late events among the three groups. CONCLUSIONS: The mid- to long-term outcomes after endovascular repair, hybrid arch repair, and open surgical repair for type B dissection involving the aortic arch (B1-2, D) were favorable and comparable in selected patients. Extensive experience and multidisciplinary teamwork are prerequisites for individualized strategies for repair of B1-2, D.

HTAADVar: Aggregation and fully automated clinical interpretation of genetic variants in heritable thoracic aortic aneurysm and dissection.

PURPOSE: Early detection and pathogenicity interpretation of disease-associated variants are crucial but challenging in molecular diagnosis, especially for insidious and life-threatening diseases, such as heritable thoracic aortic aneurysm and dissection (HTAAD). In this study, we developed HTAADVar, an unbiased and fully automated system for the molecular diagnosis of HTAAD. METHODS: We developed HTAADVar (http://htaadvar.fwgenetics.org) under the American College of Medical Genetics and Genomics/Association for Molecular Pathology framework, with optimizations based on disease- and gene-specific knowledge, expert panel recommendations, and variant observations. HTAADVar provides variant interpretation with a self-built database through the web server and the stand-alone programs. RESULTS: We constructed an expert-reviewed database by integrating 4373 variants in HTAAD genes, with comprehensive metadata curated from 697 publications and an in-house study of 790 patients. We further developed an interpretation system to assess variants automatically. Notably, HTAADVar showed a multifold increase in performance compared with public tools, reaching a sensitivity of 92.64% and specificity of 70.83%. The molecular diagnostic yield of HTAADVar among 790 patients (42.03%) also matched the clinical data, independently demonstrating its good performance in clinical application. CONCLUSION: HTAADVar represents the first fully automated system for accurate variant interpretation for HTAAD. The framework of HTAADVar could also be generalized for the molecular diagnosis of other genetic diseases.

Outcomes of thoracic endovascular aortic repair with chimney technique for aortic arch diseases.

Objective: This study aimed to summarize the long-term experience of using the chimney technique in thoracic endovascular aortic repair (TEVAR) for aortic arch diseases. Methods: From November 2007 to June 2021, a total of 345 consecutive patients (mean age 56 ± 11.3 years, range 28-83, 302 men) with aortic arch pathologies underwent TEVAR combined with chimney technique (cTEVAR). Their medical data and follow-up results were retrospectively reviewed and analyzed. Results: Among the 345 patients, 278 (80.6%) received single chimneys, 53 (15.4%) received double chimneys, 7 (2%) received triple chimneys, and 7 (2%) underwent cTEVAR accompanied by other techniques (two with extra-anatomical bypass, two with in situ fenestration, and three with physician modified fenestration). A total of 412 chimney stents were used, including 27 in the innominate artery (IA), 113 in the left common carotid artery, 270 in the left subclavian artery, and two in the aberrant right subclavian artery. Early type IA endoleaks were found in 38 (11%) patients, including 12 with the double or triple chimney technique. Early type II endoleak was found in nine (2.6%) patients. Early re-intervention occurred in two patients with double chimney technique, one for chimney stent migration and the other for compression of chimney stent. The 30-day mortality was 1.2% (4 in 345). During a mean follow-up of 42 ± 22 months (range 1-108 months), major stroke occurred in nine (2.6%) patients, chimney occlusion or stenosis occurred in six (1.7%), and retrograde type A aortic dissection occurred in four (1.2%). Fourteen (4.1%) patients received the secondary intervention. The all-cause mortality was 6.7% (23 in 345). Additionally, the total adverse event rate after cTEVAR was 13.9% (48 in 345). Conclusion: TEVAR with chimney technique provides a minimally invasive alternative with good chimney graft patency and low postoperative mortality during follow-up. However, the double and triple chimney techniques should be used cautiously as they seem to have a higher risk for type IA endoleak and adverse events after the operation.